In 2014, over 6 million Americans were diagnosed with a chronic non-healing wound, such as a venous ulcer, pressures sore, diabetic lower extremity ulcer, or surgical wound failure, and these generated over $25 million in related healthcare costs. Although the etiology of these wounds is multifactorial, they have common characteristics that contribute to poor healing, including inadequate growth factor expression, delayed wound revascularization and ischemia. Valitor, Inc. is developing protein-polymer therapeutics to overcome these cellular dysfunctions, thereby accelerating the rate of wound closure. We have designed our therapy to complement the standard practice of wound healing and to reduce the costly serial effort that chronic wounds typically require for debridement and clinical observation. Our patented technology enables us to enhance the in vivo stability and therapeutic efficacy of growth factors by conjugating them to linear chains of hyaluronic acid at defined ratios (i.e., valency). In this project, we will apply our multivalent conjugation platformto fibroblast growth factor-2 (mvFGF-2), a key biochemical regulator of wound healing that is currently limited in its therapeutic uses due to its short in vivo half-life. In our pilot studies,the potency of our multivalent conjugates of FGF-2 (mvFGF-2) was approximately ten-fold higher than unconjugated FGF-2, and multivalent conjugation increased the resistance of growth factors to endogenous proteases approximately 3-fold. Our overall objective in Phase I is to evaluate our multivalent conjugation platform as an enabling technology to improve the wound healing efficacy of FGF-2 and to advance mvFGF-2 as a candidate for further pre-clinical studies. In Specific Aim #1, we will determine the mvFGF-2 conjugate parameters that provide the greatest improvement to FGF-2 stability and wound healing efficacy in vivo. In Specific Aim #2, we will validate the wound healing efficacy of mvFGF-2 compared to market-approved alternatives. For these studies, we will use two in vivo models for impaired wound healing that recapitulate different wound healing dysfunctions and will be useful to our regulatory filings with the FDA. Our findings will facilitate the clinical translation of mvFGF-2 as a drug therapy when we begin Investigational New Drug-enabling studies during the next phase of this project.